Omega 3 versus Omega 6 polyunsaturated fatty acids in cardio-metabolic health Halim, M and Halim, A 10.36502/2020/hcr.6166 Title Omega 3 versus Omega 6 polyunsaturated fatty acids in cardio-metabolic health Authors Halim, M and Halim, A Type Article URL This version is available at: http://usir.salford.ac.uk/id/eprint/57516/ Published Date 2020 USIR is a digital collection of the research output of the University of Salford. Where copyright permits, full text material held in the repository is made freely available online and can be read, downloaded and copied for non- commercial private study or research purposes. Please check the manuscript for any further copyright restrictions. For more information, including our policy and submission procedure, please contact the Repository Team at: [email protected].
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O m e g a 3 ve r s u s O m e g a 6 polyuns a t u r a t e d fa t ty a cids in
c a r dio-m e t a bolic h e al t hH alim, M a n d H alim, A
1 0.3 6 5 0 2/2 0 2 0/hcr.61 6 6
Tit l e O m e g a 3 ve r s u s O m e g a 6 polyuns a t u r a t e d fa t ty a cids in c a r dio-m e t a bolic h e al t h
Aut h or s H alim, M a n d H alim, A
Typ e Article
U RL This ve r sion is available a t : h t t p://usir.s alfor d. ac.uk/id/e p rin t/57 5 1 6/
P u bl i s h e d D a t e 2 0 2 0
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Omega 3 versus Omega 6 Polyunsaturated Fatty Acids in Cardio-
Metabolic Health Halim M1*, Halim A2
1University of Salford, MSc Biomedical Science, Greater Manchester, United Kingdom 2Zhong Shan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
Corresponding Author: Michael Halim
Address: University of Salford, MSc Biomedical Science, Greater Manchester, United Kingdom; Email:
Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the
original work is properly cited.
Keywords
Omega-3, Omega-6, Polyunsaturated fatty acids, Cardiometabolic health
Abstract
Background: Cardiometabolic diseases like type 2 diabetes, metabolic syndrome, heart failure, and other
cardiovascular complications are the leading cause of mortality and morbidity across the globe. These conditions
are directly attributed to modifiable behaviors such as sedentary activity, poor diet, excessive consumption of
alcohol, or smoking. Efforts aimed towards their prevention and management are, therefore, not only essential in
the accomplishment of the healthy populations but also for eliminating the associated cost and health burdens.
Dietary change is an important approach to the promotion of cardiometabolic health. Omega 3 (C20–22 ω 3)
polyunsaturated fatty acids have pleiotropic effects on the functioning of cells, control inflammatory factors, and
cellular events in vascular endothelial cells and cardiomyocytes. The hypolipemic, anti-arrhythmic, and anti-
inflammatory properties of fatty acids offer cardioprotection. Government agencies and national heart
associations recommend increased consumption of omega 3 polyunsaturated fatty acids (PUFA) supplements and
fish to prevent cardiometabolic diseases. Purpose of the Study: The purpose of this study is to investigate the role played by ω-3 and ω-6
polyunsaturated fatty acids in promoting cardiometabolic health. Methods: The research study searched databases such as MEDLINE®, Embase, PsycINFO, CINAHL® and the
Cochrane Library for relevant research studies evaluating the function/benefits of polyunsaturated fatty acids
particularly ω-3 and ω-6 polyunsaturated fatty acids in promoting cardiometabolic functions published between
2011 and 2020. A total of 77 research studies were identified and used in the meta-analysis. Results: Results from the meta-analysis indicated that polyunsaturated fatty acids lower the risk for
cardiovascular disease by limiting inflammation of blood vessels, reducing thrombosis, increasing levels of high-
density lipoproteins, reducing levels of low-density lipoproteins, and reducing risk factors associated with
hypertension. Conclusion: Given the benefits of polyunsaturated fatty acids lower the risk for cardiovascular diseases indicted
in the meta-analysis. Therefore, human diets must contain the required amounts of PUFA due to the associated
or increases the production of oxidized linoleic acid
metabolites as well as proinflammatory eicosanoids,
which serve to activate NF-kB while at the same time
increasing proinflammatory cytokines as well as
chemokines [26,32]. In addition, the provision of
linoleic acid among individuals at risk of being
diagnosed with cardiovascular diseases reduced total
cholesterol, triglycerides, body mass index, and systolic
blood pressure after a 12 month follow up period, as
seen in (Table-1).
Fig-3:
The relative risk of coronary heart disease on the addition of linoleic acid. Increased consumption of linoleic acid reduces
coronary heart disease outcomes [33].
Table-1: Clinical data on changes in cardiovascular outcomes after the provision of linoleic acid following a 12 month follow up. A reduction in the levels of total cholesterol and triglycerides is
Otherwise minimal effects on thrombosis or coagulation
Otherwise minimal effects on thrombosis or coagulation
Endothelial function Reduces inflammation Reduces inflammation
Reduces oxidative stress Reduces oxidative stress
Manuscript no: JHCR-1-83 Volume: 1 Issue: 2 92 J Health Care and Research
Review Article
Citation: Halim M, Halim A. Omega 3 versus Omega 6 Polyunsaturated Fatty Acids in Cardio-Metabolic Health. J Health
Care and Research. 2020 Jun 27;1(2):83-100.
decrease in low-density lipoprotein and an increase in
high-density lipoprotein which is associated with
reduced incidences of coronary heart diseases.
Although there is less recent randomized clinical
trials evidence examining the effects of dietary fats on
various outcomes, a large body examining the impact
of dietary fat on lipid profiles has been reported. A
higher level of atherogenic cholesterol or cholesterol
carried in non-HDL vesicles, and LDL has been
implicated in atherosclerosis [65]. Corn olive oil
has been shown to reduce LDL and the total cholesterol
level [66]. However, the study by [8] reported no
significant effects while comparing the effects on blood
lipid after consumption PUFAs, although the study was
dominated by findings of one paper. A systematic
review by [67] also reported that the use of canola oil
reduces low-density lipoprotein but had no effect on
high-density lipoproteins. Guidelines in managing the
condition are associated with reducing the
concentrations of LDL cholesterol. The replacement of
saturated fatty acids (SFA) with PUFAs lowers
cholesterol LDL and changes the triglycerides: HDL
cholesterol level as shown in (Table-4).
Fig-9:
Effect of EPA: DHA ratios of 6:1 and 1:1 on veins. Acetylcholine levels reduce, resulting in the relaxation of veins [59].
Table-4: Changes in total cholesterol (Total-C), LDL Cholesterol, HDL cholesterol, Total-C/HDL cholesterol and TGs when diets are changed from SFA to carbohydrates( CHO), SFAs to
Monounsaturated fatty acid ( MUFA) and SFA to PUFAs [68]
increasing and a reduction being observed in HDL and
no significant differences being observed in LDL,
cholesterol, and triglycerides, as shown in (Fig-11).
The result recommending omega-3 supplementation in
lipid apheresis could have additional benefits.
The blow (Table-5) summaries the effect of PUFAs
on cardiometabolic health.
Further analysis reveals that the use of EPA and
DHA is linked to a reduction in cardiovascular
outcomes, as indicated by the relative risks across
various studies indicated below (Table-6). Individuals
who did not take EPA and DHA had higher relative
risks of developing coronary heart diseases as
compared to those using PUFA [76]. High levels of
triglycerides and lipoproteins were also observed
among those who did not take PUFA.
Fig-10:
The effects of omega-3 PUFAs on cholesterol efflux and paraoxonase 1 [74].
Manuscript no: JHCR-1-83 Volume: 1 Issue: 2 94 J Health Care and Research
Review Article
Citation: Halim M, Halim A. Omega 3 versus Omega 6 Polyunsaturated Fatty Acids in Cardio-Metabolic Health. J Health
Care and Research. 2020 Jun 27;1(2):83-100.
Fig-11:
HELP-treated patients showing differences in lipid profiles [75].
Table-5: The action of PUFA on cardiometabolic health summary [72]
Omega 3 Omega 6
Cholesterol EPA and DHA reduces levels of Low-density lipoproteins (LDL) and increases levels of High-Density Lipoproteins (HDL)
Less scientific data on the effect of omega 6 on HDL and LDL levels
Thrombogenesis Formation of protecin DX which limits the activity of cyclooxygenase 1 and 2
Inhibiting the synthesis of thromboxane A2, which affects the production of arachidonic acid, decreasing the activity of cyclooxygenase 1.
Inflammation
Activation and binding of Beta-arrestin-2, which breaks down to produce TABI, which inhibits TAKI and disrupting the remaining pathways. The presence of DHA and EPA interferes with the translocation of TLR-4, which serves to inhibit the production of cytokines.
Dietary linoleic acid increase s activity of cyclooxygenase 2 which increases the conversion of arachidonic acid to proinflammatory eicosanoid in the process reducing the concentration of arachidonic acid
Blood pressure and hypertension
Conversion of prostaglandins to arachidonic acid and subsequent release of vasodilators like nitric oxide.
Inhibition of ACE and the role of cytochrome p450 in activating nitric oxide
Manuscript no: JHCR-1-83 Volume: 1 Issue: 2 95 J Health Care and Research
Review Article
Citation: Halim M, Halim A. Omega 3 versus Omega 6 Polyunsaturated Fatty Acids in Cardio-Metabolic Health. J Health
Care and Research. 2020 Jun 27;1(2):83-100.
Table-6: A meta-analysis table – table constructed to highlight the main contents of this literature review based on thorough analysis of all the primary research, studies and data involved
Author Title Relevance to the topic
[7]
Omega-3, omega-6, and total dietary polyunsaturated fat for prevention and treatment of type 2 diabetes mellitus: Systematic review and meta-analysis of randomized controlled trials.
[7] established elevated LDL-cholesterol as atherosclerosis and CVD risk factor. The research that they conducted demonstrated that increased ω-3 and ω-6 intake had hypocholesterolaemia effects. However, the information provided in their study concerning the specific effects of ω-6 PUFA on blood lipid profiles is limited.
[1] Polyunsaturated fatty acids for the primary and secondary prevention of cardiovascular disease
Most of the RCT data used by [1] in his study to determine the effects of PUFAs on cardiometabolic diseases was quite old. From his findings, replacement of 5% SFAs by PUFAs significantly reduced CAD risks.
[6] Overweight, obesity, and risk of cardiometabolic multimorbidity
[6] in their work, conducted a Cochrane meta-analysis where they examined SFA intake reduction and replacing it with PUFA or MUFA. Their research concluded that replacement of SFAs with ω-3 and ω-6 PUFAs resulted in a 17% reduction in cardiometabolic events. They reported that, replacing some saturated fats with PUFAs having plants origin resulted yielded lower cardiometabolic disease risk. Subgroup analysis conducted showed lower risks in PUFA compared to SFA groups.
[11] Biochemical mechanism of the ratio of omega 6 to 3 fatty acids on blood lipid reduction
[11] literature is relevant to this study, where they conducted a crossectional analysis of Spanish men considered obese. The men underwent laparoscopic gastric bypass surgery. Analysis of the abdominal adipose tissue and venous blood serum was conducted to calculate FA composition. A positive correlation of ω-6 PUFAs with HDL-C and an inverse correlation with triglycerides (TG) was found.
[13] The ratio of dietary ω-3 and ω-6 fatty acids independent determinants of muscle mass in hemodialysis patients with diabetes.
[13] conducted observational studies among the East Asian and Asian Indian population, which is relevant to this study. They found out through research that, omega 6 PUFAs to be inversely associated with TG across the population studied. A cross-sectional analysis conducted on male cohort found serum LA to be positively associated with HDL-C particle size and inversely associated with LDL-C and VLDL particle sizes.
[15] A systematic review of the effect of dietary saturated and polyunsaturated fat on heart disease
[15] carried out a meta-analysis of 80 controlled interventional trials where they concluded that n-6 PUFA has beneficial effects on blood lipid levels. The total PUFAs can be considered to be equal to omega 6 PUFA with a number of 18 carbons.
[22]
Inflammatory markers and extent and progression of early atherosclerosis: Meta-analysis of individual-participant-data from 20 prospective studies of the PROG-IMT collaboration.
Their research associated a reduction in blood pressure with a reduction in CVD risks. They concluded in their research that dietary LA is inversely associated with blood pressure (BP)
[29]
The associations of serum n-6 polyunsaturated fatty acids with serum C-reactive protein in men: The Kuopio Ischaemic Heart Disease Risk Factor Study
Cardiometabolic conditions are directly attributed to modifiable behaviors such as sedentary activity and poor diet. Omega 3 (C20–22 ω 3) polyunsaturated fatty acids have pleiotropic effects on the functioning of cells, control inflammatory factors and cellular events in vascular endothelial cells and cardiomyocytes. The hypolipemic, anti-arrhythmic, and anti-inflammatory properties of fatty acids offer cardioprotection.
Manuscript no: JHCR-1-83 Volume: 1 Issue: 2 96 J Health Care and Research
Review Article
Citation: Halim M, Halim A. Omega 3 versus Omega 6 Polyunsaturated Fatty Acids in Cardio-Metabolic Health. J Health
Care and Research. 2020 Jun 27;1(2):83-100.
Conclusion
Cardiometabolic diseases are significant health and
economic burden globally since they contribute to
preventable mortality and morbidity in individuals of
all ages, races, and genders. One of the most effective
approaches towards the prevention and management
of cardiometabolic diseases include lifestyle and
dietary changes. Based on the meta-analysis, ω-3 and
ω-6 PUFAs are essential fatty acids in the body
functioning, and since they are not synthesized in the
human body, they are mostly consumed through the
dietary sources and nutritional supplements. The
significance of ω -3 PUFAs on cardiometabolic is clear
that is the reduction of inflammation agents that may
contribute to metabolic syndrome as well as being
essential in the prevention of cardiovascular diseases
like thrombosis. Similarly, ω-6 PUFAs are important in
the promotion of cardiovascular health by lowering
cholesterol levels. Despite the highlighted benefits of
the two fatty acids on cardiometabolic health, a
significant controversy relates to the question as to
whether ω-6 PUFAs contribute to inflammation or not.
For instance, the conversion of SFA to PUFAs is always
associated with a brisk of increasing inflammation.
Omega 3- and 6 fatty acids have also been indicated to
compete for substrates, and as a result, omega-3 is
linked with anti-inflammatory behavior while omega-6
is linked with proinflammatory behavior. Also, the
formation of omega-6 fatty acids is associated with the
release of inflammatory molecules such as
leukotrienes. The effect of downstream products
produced by omega-3 and omega-6 fatty acids in
relation to inflammation also remains unknown, while
other studies suggest that inflammation linked to
omega-6 could be explained by the highomega-3 to
omega 6 ratios. Thus, there is a need to carry out more
research on the link between omega-6 PUFAs and
inflammation with specific emphasis being placed on
the exact mechanism.
References
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Keywords: Omega-3, Omega-6, Polyunsaturated fatty acids, Cardiometabolic health Manuscript no: JHCR-1-83 Volume: 1 Issue: 2 100 J Health Care and Research
Review Article
Citation: Halim M, Halim A. Omega 3 versus Omega 6 Polyunsaturated Fatty Acids in Cardio-Metabolic Health. J Health
Care and Research. 2020 Jun 27;1(2):83-100.
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